What is the suppressing effect of the PPAR-gamma ligands on stomach cancer cells?

PPAR- gamma is manifested in a variety of tissues and cancer cells and the ligands that activate PPAR- PPAR- are currently being studied as a novel treatment. The PPAR-gamma ligand generally decreases the survival rate of cancer cells via differentiation, apoptotic induction, and changes in genes or proteins associated with entrance into the G1/S phase. There have been some reports suggesting that stomach cancer cells manifest PPAR- gamma and are suppressed by the PPAR- gamma ligand. Recently, another report has shown that troglitazone, the ligand of PPAR- gamma , may prove useful in preventive medicine, and this effect is dependent on PPAR- gamma . A research article to be published in volume 15 on January 21, 2009 in the World Journal of Gastroenterology addresses this point. A research team led by Professor DH Kim from the Medical Research Institute, Pusan National University Hospital, Korea found that the reaction of the PPAR- gamma agonist pathway on PPAR- gamma , troglitazone, suppresses the proliferation of colon cancer cells, and induces apoptosis, and expression of the growth response-1 gene in early phase. These processes are activated downstream of the suppression one by one via a PPAR- gamma -independent pathway. Moreover, an inductive chemical compound associated with CDDO causes PPAR- gamma -dependent caveolin expression and a PPAR- gamma -independent induction of the apoptosis reaction.

This report shows that ciglitazone and troglitazone suppress the proliferation of stomach cancer cells via the arrest of G1 phase. The arrest of G1 phase was reported in colon cancer cells via activation of PPAR- gamma. Also, each of the stomach cancer cell types which demonstrated p53 mutations were suppressed more strongly by troglitazone than by ciglitazone, and this effect was more evident in the SNU-668 than in the SNU-216 cells. SNU-668 cells demonstrated p53 and ras mutations, and it will be necessary in future studies to clarify the relationship between these results and the underlying mechanisms. This means that the concentrations of troglitazone that are used clinically suppress the growth of stomach cancer cells, and this may be used as a method to target therapy of gastric cancer.

Source: World Journal of Gastroenterology